Method of producing an epidural nerve block

ABSTRACT

AN ANALGESIC METHOD OF REDUCING PAIN BY AN EPIDURAL NERVE BLOCK WHICH COMPRISES INJECTING INTO THE EPIDURAL SPACE IN THE BODY OF A PATIENT A COMPOSITION CONTAINING WATER, A SUGAR OR SUGAR DERIVATIVE AND A POTASSIUM SALT, AND SHORTLY THEREAFTER INJECTING IN THE SAME AREA, AN AQUEOUS SOLUTION OF A SUGAR OR SUGAR DERIVATIVE AND CALCIUM GLUCONATE.

United States Patent US. Cl. 424-128 1 Claim ABSTRACT OF THE DISCLOSURE An analgesic method of reducing pain by an epidural nerve block which comprises injecting into the epidural space in the body of a patient a composition containing water, a sugar or sugar derivative and a potassium salt, and shortly thereafter injecting in the same area, an

aqueous solution of a sugar or sugar derivative and calcium gluconate.

This application is a continuation-in-part of my co pending patent application Ser. No. 814,169, filed on Apr. 7, 1969, now abandoned.

In the conventional surgery the post-operative pains at the breast, abdomen, extremities, etc. and pains at the last stage of cancer in the above-mentioned regions are relieved either by general or local anesthesia.

In the case of general anesthesia a narcotic is used to act on central nervous system to paralyze'them, but it deprives a patient of its kinetic functions as well as sensory. In the case of local anesthesia a narcotic is administered to peripheral nerve tissue to dull or paralyze them but, in this case also local motor functions are often deprived. Furthermore, narcotics of this sort are inevitably not physiological but leave unfavourable effects on the living body. If a narcotic is used for painless delivery it prolongs delivery time and exposes the newborn to the danger of asphyxia and other complications.

One object of the invention is accordingly to provide a new type of anodyne and analgesic method free from unphysiological materials like narcotics.

Another object of the invention is to provide an anodyne and analgesic method with neither unfavourable effects nor complications on the human body.

A further object of the invention is to induce an effective blockade of pain conductive nerve function without affecting motor nerve function.

A further object of the invention is to provide an anodyne and analgesic method for painless delivery in which it becomes possible to avoid delayed delivery time and exposure of newborn to further dangerous complications.

The above and other objects of the invention will be apparent from the description as follows.

The anodyne of the invention comprises an aqueous solution having a sugar or sugar derivative concentration of 5 to 20 percent by weight and having dissolved therein at least one species selected from the group consisting of potassium phosphate and potassium chloride in a potassium ion concentration of between 0.2 and 3.0 meq. per ml. of the solution.

According to the invention, the anodyne as above is ice injected into epidural space in an amount of between 5 ml. and 50 ml., whereby the pain of a patient can be relieved free of secondary effects and hindrance of kinetic functions.

The theory of analgesic action according to the invention is as follows. When the anodyne of the invention is injected into epidural space, the amount of potassium ion extraneuronal tissue increases. It causes, after a slight initial depolarization, hyperpolarization of the resting membrane potential which elevates the threshold value for action potential generated by impulse (pain). Smaller nerves receive the above effects more strongly, and so smaller nerves that conduct pain should be completely free from the generation of action potential, and thus, nerve conduction of pain is blocked. On the other hand, larger nerves are not noticeably affected and thus, kinetic functions are scarcely hindered. The pain of a patient is thus relieved without disturbance of kinetic functions. The anodyne of the invention does not have harmful effects on the human body since it is composed of substances which are physiologically in the human body and its action is due to a modification of the mechanism occurring in normal human body.

According to the invention, the concentration of potassium ion in the anodyne should be in the range of 0.2 to 3.0 meq. per 10 ml. solution. A concentration lower than 0.2 meq. will not exhibit a suflicient analgesic effect, and when higher than 3.0 meq., it will diminish kinetic functions. A recommended concentration of potassium ion is in the range of 0.4 to 1.5 meq. per 10 ml. solution.

As a source of potassium ion, potassium phosphate, e.g., KH PO K HPO etc. and potassium chloride are used, respectively or in combination. Potassium phosphate (KH PO is particularly desirable since when an H PO ion generated in the solution is introduced into the epidural space it acts as weak buffer and prevents the fall in the pH of the solution. The pH of the anodyne of the invention is desirably in the vicinity of that of body fluid, generally in the range of 7.30 to 7.45.

Another component of the anodyne of the invention, sugars or sugar derivatives, serves to decrease the amount of potassium ion due to its repolarizing action accompanying potassium uptake into cell. When solvents other than solutions of sugars or sugar derivatives are used, potassium ion concentration would be more than 3.0 meq./ 10 ml. to exhibit sufficient analgesic effects, which, however, is presumed to induce some inevitable degree of decrease in motor function. Preferred sugars or sugar derivatives are sorbitol, xylitol, fructose, glucose and dextran of an average molecular weight of 50,000 to 100,000, and sorbitol is most desirable for the purpose above-mentioned. These sugars or sugar derivatives may be used alone or in mixture with one another. The sugar or sugar derivative concentration of 5 to 20 weight percent is suitable, preferably 8 to 15 weight percent.

The anodyne of the invention can be easily prepared by adding either or both potassium phosphate and potassium chloride in an aqueous solution of a sugar or sugar derivative in distilled water.

The anodyne of the invention is injected into the epidural space, generally at the interspace between the first and the second, the second and the third, the third and the fourth, or the fourth and the fifth lumbar vertebras. The amount of injection may vary according to the nature and intensity of pain, generally ranging from ml. to 50 ml., and 15 ml. to 35 ml. is recommendable. The anodyne may be injected at one time or partially in succession.

The anodyne of the invention is effective in relieving various pain afllictions complained of by various patients, and particularly etfective in the relief of pains experienced in delivery, post-operative pains at the breast, abdomen, extremities, etc., pains at the last stage of cancer, and pains from rheumatism of leg joints at the lower back.

The anodyne of the invention exhibits fairly durable analgesic eflects and the effective duration is not always proportionate to the increase of the amount of introduced potassium ion but it generally remains elfective for about 1 to 6 hours.

According to the researches by the present inventor it has been found that by injecting calcium ion into the epidural space in addition to the administration of the above anodyne of the invention the analgesic effect of the anodyne of the invention is of a longer duration.

The theoretical basis for the long-lasting elfect obtainable by the addition of calcium ion is believed to be that the increased amount of calcium ion in extraneuronal tissue of the epidural space covers ionic channels through which inflow of sodium ion into the nerve cell occurs during depolarization and thus excitement of nerve cells (pain) can hardly occur.

For the above purpose an aqueous solution of calcium gluconate or an aqueous solution of a sugar or a sugar derivative containing said calcium gluconate is used.

For convenience, the anodyne of the invention containing potassium ion will be hereinafter referred to as solution I, and said calcium gluconate solution as solution II.

The calcium ion concentration in solution II is desiraably in the range of 5 to 30 meq. per ml. of the solution and particularly desirable is 10 to 20 meq. per 10 ml. of the solution. As the sugars or sugar derivatives sorbitol, xylitol, fructose, glucose and dextran of an average molecular weight of 50,000 to 100,000 are desirable, and these sugars or sugar derivatives may be used singly or in mixture. A sugar or a sugar derivative concentration of 5 to 20 Weight percent is desired. Said solution II can be easily prepared by dissolving calcium gluconate in distilled water or in a distilled water solution of sugar or a sugar derivative.

Said solution 11 is, as above described, injected into the epidural space within 1 to 5 minutes after injection of the solution I into the epidural space. If said injection of the solution II is delayed in the above case, a longlasting analgesic effect by the calcium ion will not be obtainable. The injection of the solution II should be within 2 to 3 min. after the injection of the solution I. When the solution I is injected in several successive doses the time of injection of the solution II should be calculated from the injection of the last dose. The preferred amount of injection of the solution II is 5 to 50 ml.

The solution II also physiologically acts on nerves, and as far as applied in the above-described range of amount, it will have no' harmful effects on the human body nor depress kinetic functions. In painless delivery, the use of this solution II will not afiect the delivery time nor will bring the danger of asphyxia to the newborn.

For better understanding of the invention clinical examples will be given hereinafter.

CLINICAL EXAMPLE 1 A 26-year-old primipara in the third week of terminal month of her pregnancy was injected at the epidural space between second and third lumbar vertebras, with ml. of 15 weight percent of an aqueous sorbitol solution of potassium phosphate (KH PO in a potassium ion concentration of 1.4 meq. when two fingers were passable in her external os of uterus. She had been suffering from labor afiiiction, but 4 minutes after the administration of the potassium phosphate solution she became released from the pain due to labor. At this time she was injected at the same space with 10 ml. of a 10 weight percent aqueous sorbitol solution of calcium gluconate in a calcium ion concentration of 5 meq. which might be.expected to prolong the duration of the analgesia induced by the potassium phosphate solution. She gave birth to a baby with full scores in Apgars 3 hours later without labor pain.

CLINICAL EXAMPLE 2 A pregnant patient aged 33 who received a cesarean section was injected, at the epidural space between the second and third lumbar vertebras, with 10 m1. of a 10 weight percent aqueous sorbitol solution of potassium phosphate (KI-I PO with a potassium ion concentration of 0.2 meq. 3 minutes later, she was given, at the same space, 10 ml. of a 10 weight percent aqueous sorbitol solution of potassium phosphate QKH POQ in a potassium ion concentration of 0.6 meq. 3 minutes later, she was injected, at the same space, with 2.0 ml. of a 10 Weight percent aqueous sorbitol solution of calcium gluconate in a. calcium ion concentration of 20 meq. The effect of the analgesics was observed to be satisfactory with a rapid onset of action and lasted for more than 3 hours. Em-

barrassment of the patient due to postoperative pain affliction never recurred even after the analgesic effect of these solutions was considered to have faded out.

CLINICAL EXAMPLE 3 The patient was a woman of 32 years old with suspected diagnosis of intestinal obstruction when laparotomy revealed a very large pancreatic cyst.

After the conclusion of the operation, in order to prevent the incidence of postoperative pain she was injected, at the epidural space between the second and third lumbar vertebras, with a 10 ml. of 10 weight percent aqueous sorbitol solution, of potassium phosphate (KH PO in a potassium ion concentration of 0.2 meq. 3 minutes later, she was given, at the same space, 10 ml. of a 10 weight percent aqueous sorbitol solution of potassium phosphate (KH PO in a potassium ion concentration of 0.6 meq. Further 3 minutes later, she was injected, at the same space, with 2.0 ml. of a 10 weight percent aqueous sorbitol solution dissolving calcium gluconate in a calcium ion concentration of 20 meq. Analgesia showed rapid onset and suflicient progress and continued for more than 10 hours after the operation. Another similar quantity of these solutions required the next day was enough to remove the problems of postoperative pain afiiiction of this patient during her whole postoperative course.

CLINICAL EXAMPLE 4 An epidural puncture was performed between L and L vertebras in a patient aged 28 who was in the third terminal month of her pregnancy and was suifering from pain due to labor for two hours.

She was administered 15 ml. of a 15 weight percent aqueous sorbitol solution containing potassium phosphate (KH PO in a potassium ion concentration of 1.2 meq. and 3 minutes later 20 ml. of 10 weight percent aqueous dextran (average molecular weight of 75,000) solution containing calcium gluconate in a calcium ion concentra- I tion of 20 meq. was injected at the same space. Thus she was released from the pain affliction.

The duration of the analgesic etfect of these agents lasted for more than 3 hours and she was delivered without complications of a healthy female infant 3 hours after the administration of these agents.

I claim:

1. An analgesic method of reducing pain by an epidural nerve block which comprises injecting into the epidural space in the body of a patient suffering from said pain, from 5 to 50 ml. of a solution comprising water, from 5% to 20% by weight of a sugar or sugar derivative selected from the group consisting of sorbitol, xylitol, fructose,

glucose and dextran having an average molecular weight of 50,000 to 100,000 and a potassium compound selected from the group consisting of dipotassium hydrogen phosphate, potassium dihydrogen phosphate and potassium chloride, said potassium compound being present in an amount to provide a potassium ion concentration of 0.2 to 3.0 meq. per 10 ml. of said solution, and then within one to five minutes after injection of said solution, injecting in the same injection site from 5 to 50 ml. of a solution comprising water, from 5% to 20% by weight of a sugar or sugar derivative selected from the group consisting of sorbitol, xylitol, fructose, glucose and dextran having an average molecular weight of 50,000 to 10,000 and calcium gluconate in an amount suflicient to provide a The dispensatory, p. 228, 26th edition, 1967. Physicians Desk Reference, 22nd edition, 1967, pp. 798, 799

Merck Index, 1968, pp. 857,971, 972.

10 ALBERT T. MEYERS, Primary Examiner N. A. DREZIN, Assistant Examiner US. Cl. X.R. 424153, 154 

